Lymphoid follicle formation in sinus mucosa of chronic sinusitis

Abstract

While the presence of mucosa-associated lymphoid tissue (MALT) in the human upper respiratory mucosa is still being debated, it is known that lymphoid follicles (LFs) are present in the mucosa of patients with chronic sinusitis. In the present study, we investigated LFs in chronic sinusitis mucosa samples for the first time immunohistochemically to reveal the frequency and process of lymphoid follicle formation. Forty maxillary sinus mucosa samples from 27 surgical cases were examined. Of the 31 samples, 15 (48.4%) contained primary and/or secondary LFs, 27 (87.1%) contained lymphocyte aggregates (LAs), and 27 (87.1%) contained high endothelial venules (HEVs) located in the LAs and around the LFs. In the inflammatory site above the lesion of the LAs or LFs, respectively, intraepithelial lymphocyte infiltration and a non-ciliated structure or lympho epithelium were seen. In the first phase of diffuse lymphocyte infiltration, CD8+ T cells (suppressor/cytotoxic) were the predominant cells observed in a spreading pattern under the epithelium. In the next phase, while OPD4+ T cells (helper/inducer) were infiltrating, L26+ B cells were gradually aggregating to form lymphocyte clusters (LCs). S-100+ antigen-presenting cells and DRC+ follicular dendritic cells (FDCs) had already appeared during lymphocyte aggregation to promote lymphoid follicle formation. The region of LFs was morphologically divided into the lympho epithelium (LE), the sublympho epithelial area (SLA), the parafollicular area (PFA), and the follicular area (FA). The LE was invaded focally by L26+ B cells and sporadically by UCHL1+ T cells. In the SLA, L26+ B cells and small numbers of OPD4+ T cells were dominant. In the PFA, both OPD4+ and CD8+ T cells were present. The FA consisted of B cells, FDCs, and a few OPD4+ T cells in germinal centers (GCs). In the GCs, we observed VLA-4+ lymphocytes, VCAM-1+ FDCs, IgM+ B cells, and a few IgA+ B cells. On the basis of this study, LFs with lympho epithelium and HEVs are considered prevalent pathological findings in the mucosa humans with chronic sinusitis. Immunohistochemical study revealed the infiltration patterns of T and B lymphocyte subpopulations and FDCs, which clarified the process of LAs, LCs and LFs. This study confirms that LFs are immunologically activated areas that produce plasma cells and are supported by the cellular interaction between FDCs and B cells in their GCs. These MALTs in chronic sinusitis play an important role in mucosal immunity and persistent local inflammation.